Perturbation of Retinoid Homeostasis Increases Malformation Risk in Embryos Exposed to Pregestational Diabetes

Pregestational diabetes is highly associated with an increased risk of birth defects. However, factors that can increase or reduce the expressivity and penetrance of malformations in pregnancies in women with diabetes remain poorly identified. All-trans retinoic acid (RA) plays crucial roles in embryogenesis. Here, we find that Cyp26a1, which encodes a key enzyme for catabolic inactivation of RA required for tight control of local RA concentrations, is significantly downregulated in embryos of diabetic mice. Embryonic tissues expressing Cyp26a1 show reduced efficiency of RA clearance. Embryos exposed to diabetes are thus sensitized to RA and more vulnerable to the deleterious effects of increased RA signaling. Susceptibility to RA teratogenesis is further potentiated in embryos with a preexisting genetic defect of RA metabolism. Increasing RA clearance efficiency using a preconditioning approach can counteract the increased susceptibility to RA teratogenesis in embryos of diabetic mice. Our findings provide new insight into gene–environment interactions that influence individual risk in the manifestation of diabetes-related birth defects and shed light on environmental risk factors and genetic variants for a stratified medicine approach to screening women with diabetes who are of childbearing age and assessing the risk of birth defects during pregnancy.

Diabetes Complications


Perturbation of Retinoid Homeostasis Increases Malformation Risk in Embryos Exposed to Pregestational Diabetes was first posted on April 11, 2017 at 5:16 am.
©2013 “DIABETICS DIET“. Use of this feed is for personal non-commercial use only. If you are not reading this article in your feed reader, then the site is guilty of copyright infringement. Please contact me at jmagcase@gmail.com

Reblogged 1 month ago from diabeticscareguide.com

Published by

Amrita Wellness Medicine Clinic

Alina Porojan has been working as a natural medicine practitioner for the past twelve years, constantly educating herself and deepening her knowledge and clinical experience. Alina believes that health and healing is inherent to each of us, and sees her role as re-connecting us to our already existing potential for optimal health and wellness.